Clinical Evaluation - A Phase IIA Proof of Concept Study of Regorafenib (Bayer 73-4506) in Biopsy-amenable Asian Colorectal Cancer Patients
- Histologically or cytologically proven metastatic colorectal adenocarcinoma that is
refractory to standard therapy and not amenable to surgery with curative intent.
- Tumor characteristics:
- At least one lesion that is suitable for a repeated biopsy; eg. subcutaneous
nodule, skin lesion, rectal tumor, colonic mass easily reached by colonoscopy,
peritoneal masses at least 3cm in maximum diameter that are easily assessable by
image guided core biopsy.
- For liver lesions, more superficially located lesions at least 3cm in maximum
dimension with a rim of normal liver tissue, assessable safely by image guided
core biopsy as determined by an experienced interventional radiologist.
- Eastern Cooperative Oncology Group ECOG performance status of 0 or 1 (see Appendix
- Adequate bone marrow function (absolute neutrophil count =1,500/mm3; platelet count
=100000/mm3; hemoglobin =9g/dl
- Adequate liver and renal function as assessed by the following laboratory
requirements conducted within 7 days of starting to study treatment:
- Total bilirubin < 1.5 x the upper limit of normal (ULN).
- Alanine transaminase (ALT) and aspartate aminotransferase (AST) < 2.5 x ULN (< 5
x ULN for patients with liver involvement of their cancer).
- Amylase and lipase < 1.5 x the ULN
- Serum creatinine < 1.5 x the ULN.
- Glomerular filtration rate (GFR) = 30 ml/min/1.73 m2 according to the MDRD
(Modified diet in renal disease) abbreviated formula
- Prothrombin time, international normalized ratio (INR) and partial thromboplastin
time less than or equal to 1.2 times the ULN.
- Male or female at least 21 years of age.
- A female subject is eligible to enter and participate in the study if she is:
- Non-childbearing potential (ie. physiologically incapable of becoming pregnant)
including any women who:
- Has had a hysterectomy or
- Has bilateral oophorectomy (ovariectomy) or
- Has bilateral tubal ligation or
- Is postmenopausal (demonstrate total cessation of menses for greater than or
- Childbearing potential, has a negative serum or urine pregnancy test at
screening, agrees to one of the following: double barrier contraception or
- Predicted life expectancy of at least 12 weeks.
- Resting oxygen saturation greater than 92% on room air.
- Written informed consent.
- Able to swallow and retain oral medication.
- Prothrombin time (PT), International Normalized Ratio for PT (PT INR), and partial
thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) within